AUTHOR=Leung Daniel , Cohen Carolyn A. , Mu Xiaofeng , Rosa Duque Jaime S. , Cheng Samuel M. S. , Wang Xiwei , Wang Manni , Zhang Wenyue , Zhang Yanmei , Tam Issan Y. S. , Lam Jennifer H. Y. , Chan Sau Man , Chaothai Sara , Kwan Kelvin K. H. , Chan Karl C. K. , Li John K. C. , Luk Leo L. H. , Tsang Leo C. H. , Chu Nym Coco , Wong Wilfred H. S. , Mori Masashi , Leung Wing Hang , Valkenburg Sophie , Peiris Malik , Tu Wenwei , Lau Yu Lung TITLE=Immunogenicity against wild-type and Omicron SARS-CoV-2 after a third dose of inactivated COVID-19 vaccine in healthy adolescents JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1106837 DOI=10.3389/fimmu.2023.1106837 ISSN=1664-3224 ABSTRACT=Introduction

Two doses of inactivated SARS-CoV-2 vaccine CoronaVac cannot elicit high efficacy against symptomatic COVID-19, especially against the Omicron variant, but that can be improved by a third dose in adults. The use of a third dose of CoronaVac in adolescents may be supported by immunobridging studies in the absence of efficacy data.

Methods

With an immunobridging design, our study (NCT04800133) tested the non-inferiority of the binding and neutralizing antibodies and T cell responses induced by a third dose of CoronaVac in healthy adolescents (N=94, median age 14.2 years, 56% male) compared to adults (N=153, median age 48.1 years, 44% male). Responses against wild-type (WT) and BA.1 SARS-CoV-2 were compared in adolescents. Safety and reactogenicity were also monitored.

Results

A homologous third dose of CoronaVac further enhanced antibody response in adolescents compared to just 2 doses. Adolescents mounted non-inferior antibody and T cell responses compared to adults. Although S IgG and neutralizing antibody responses to BA.1 were lower than to WT, they remained detectable in 96% and 86% of adolescents. T cell responses to peptide pools spanning only the mutations of BA.1 S, N and M in adolescents were preserved, increased, and halved compared to WT respectively. No safety concerns were identified.

Discussion

The primary vaccination series of inactivated SARS-CoV-2 vaccines for adolescents should include 3 doses for improved humoral immunogenicity.